Method: Since the Allergic Diseases Clinical Laboratory was computerized in 1991, creating a searchable database for all laboratory patient investigations, we have performed 210 placebo-controlled dye and preservative challenges in 202 individual patients [193 adults, 9 children] presenting primarily with urticaria, angioedema, and meal-related gastrointestinal symptoms. The challenges were carried out by first presenting a series of blinded liquid doses, some of which contained a mixture of FD&C Blue #1 and Blue #2, Red #3 and Red #40, and Yellow #5 & #6. The initial dye dosing was with 0.2% solutions, and if these were negative, 2% solutions were then presented. If there was no reaction to the dye solutions and placebos, we then administered a mixture of preservative compounds [sodium benzoate, p-hydroxybenzoic acid, butylated hydroxyanisole, and butylated hydroxytoluene] or placebos in capsule form, with early dosing at 4 capsules of 50 mg of the preservative mix, and later dosing with 4 capsules of 250 mg of the preservative mix.
Results: We documented only 4 positive challenges in this series of 210, and two of those were not reproducible in repeat challenges conducted on subsequent days. There were 40 placebo responders. Three of the four positives appeared to be related to the dyes. In the one dye-reactor that was reproducible, the causative dye appeared to be one of the two blue dyes.
Conclusions: We conclude that taken together, dyes and preservatives are frequently suspected but rarely actually participate as triggers of urticaria and angioedema.